How Effective Are Interventions Targeting Depression in Chronic Pain?

No one depression intervention type has demonstrated its superiority in populations of patients living with differing types of chronic pain, according to research results published in Pain Medicine.

Researchers conducted a systematic review to evaluate the current interventions used to treat depressive symptoms in people living with chronic pain. In particular, the researchers sought to determine which clinical interventions have an effect on depressive symptoms in chronic pain, and what the effects of these clinical interventions are.

Databases were searched through September 15, 2020. Systematic reviews that focused on adult patients with chronic pain lasting for 3 or more months were included. Outcome scales of interest included the Beck Depression Inventory, the Hamilton Depression Rating, the Montgomery-Asberg Depression Rating, and the Centre for Epidemiological Studies Depression Scales.

A total of 8435 studies were retrieved and screened. After review and application of exclusion criteria, a total of 83 reviews remained. The reviews synthesized depression outcomes across 459 unique primary studies published between January 1981 and November 2018. Study sample sizes ranged from 24 to 6478 participants.

Twelve percent of reviews were rated high quality, while l16% and 24% were moderate and low quality, respectively; 48% of reviews were of critically low quality, with issues including no list of reasoning for the exclusion of full-text articles, no investigation into causes of heterogeneity, and no investigation into publication bias.

Eight common pain types were identified: arthritis (including osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis), axial pain (chronic low back and neck pain), fibromyalgia, chronic headache, musculoskeletal, neuropathic, orofacial (temporomandibular joint disorder), and mixed or unspecified pain.

Across 83 reviews, fibromyalgia, mixed chronic pain, and arthritis were the most common types of pain evaluated (35%, 28%, and 16%, respectively), with psychological, pharmacological, and mind-body as the most common intervention types (45%, 18%, and 15%, respectively). Through a network visualization, “distinct subgroups” began to form based on pain and intervention types.

The largest network included 37 reviews focused on psychological interventions. Within this network, 1 high-quality review compared ACT in mixed chronic pain with inactive comparators over medium-length follow up, and reported the largest significant point estimate (standardized mean difference [SMD], -0.71; 95% CI, -1.09 to -0.33). Another synthesis reported a “significant medium effect” of web-based psychotherapy in reducing depressive symptoms in fibromyalgia with mixed comparators (SMD, -0.51; 95% CI -0.87 to -0.15).

Another network—this one including mind-body, exercise, massage, and water therapy—examined effects in patients with fibromyalgia and mixed chronic pain. The most significant effect in reducing depressive symptoms was from a moderate-quality review of mediation with mixed comparators; the review synthesized 6 randomized controlled trials including 658 participants (SMD, -0.49; 95% CI, -1.89 to -0.1), and mindful movement was found to have small to medium effects.

A network focused on exercise included reviews specific to fibromyalgia, arthritis, and musculoskeletal pain. A single meta-analysis of 9 RCTs with 876 participants reported on a small but significant effect of exercise-based rehabilitation for arthritis (SMD, -0.16; 95% CI, -0.29 to -0.02). Two reviews of low and critically low quality evaluated the role of massage therapy in fibromyalgia, while a moderate quality review evaluated water-based interventions. Small effects were shown on depressive symptoms for balneotherapy vs inactive comparators over medium- long-term follow-up (SMD, -0.31; 95% CI, -0.59 to -0.03).

No overlap was observed between the main network and the pharmacological network. Sixteen reviews that evaluated pharmacotherapy displayed a dichotomy of quality: 53% were critically low quality, while 33% were high quality. Analyses evaluated anti-depressants including selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, mirtazapine, gabapentinoids, and quetiapine.

Gabapentinoids showed a larger effect in patients with neuropathic pain vs fibromyalgia, while SSRIs demonstrated small to medium significant effect sizes in patients with fibromyalgia only.

Numerous systematic reviews of low or critically low quality evaluated the effects of brain stimulation, music, complementary and alternative medicine, acupuncture, cannabis, and interventional therapy. One moderate quality review evaluated the effects of brain stimulation in those with neuropathic pain, while the other moderate quality review investigated the combination of herbal Chinese medicines with pharmacological interventions in arthritis. Effects were small to medium and small, respectively, and nonsignificant in both studies.

Investigators then reviewed the distribution of effects by pain type. In fibromyalgia, effects of pharmacological, mind-body, and mixed psychological interventions were reviewed; chronic pain analyses investigated psychological interventions like ACT and web-based therapy, as well as cognitive and behavioral interventions.

Arthritis analyses focused on psychoeducation and mixed psychological interventions, axial pain analyses focused on behavioral, multidisciplinary, self-regulatory psychological interventions, and mind-body interventions, neuropathic pain evaluated pharmacological interventions vs inactive comparators and brain stimulation, and headache analyses—of which there were only 2—investigated the effects of web-based psychological interventions.

Study limitations include the limited focused on depressive symptoms, a lack of well-defined intervention types, and grouping of pain types based on the definitions included in the reviews.

“Effects on depressive symptoms so far have been under synthesized in common pain interventions such as opioids and acupuncture,” the researchers concluded. “There is also a need for more assessment and synthesis of depression outcomes in common pain conditions such as arthritis and axial pain.”


Cheng DK, Lai KSP, Pico-Espinsoa OJ, et al. Interventions for depressive symptoms in people living with chronic pain: A systematic review of meta-analyses. Pain Med. Published online August 9, 2021. doi:10.1093/pm/pnab248